The tissue responsible for attachment of the gingiva to teeth is the junctional epithelium. This interface is vitally important as the site of initiation of periodontal diseases. Migration of the junctional epithelium in an apical direction along a tooth results in the pockets associated with periodontal disease. After therapy, many diseased sites heal by the formation of a long junctional epithelial attachment to the tooth rather than the regeneration of a new connective tissue periodontal attachment. The objective of this study is to examine the mechanisms by which components of the extracellular matrix may influence the attachment and migratory behavior of junctional epithelial cells using a rat model system. The hypothesis to be tested is that molecular signals (peptide and carbohydrate) from the basement membrane are largely responsible for the unique phenotype of junctional epithelial cells. These signals may be important determinants of the formation of a long junctional epithelial attachment. The biologically active extracellular matrix constituents fibronectin, laminin, type VIII collagen and heparan sultate proteoglycan, and their carbohydrate components are likely to play important roles in the behavior of junctional epithelium. The first aim of the proposed studies is to determine, in vitro, the role played by fibronectin, laminin, type VIII collagen and heparan sulfate proteoglycan in the initial adhesion, spreading and either stable attachment or migration of junctional epithelium and periodontal ligament fibroblasts. The second aim of the proposed studies will be to assess the means by which the carbohydrate moieties present on the molecules examined in aim I may influence cell behavior, in vitro. The third aim is to determine how molecules identified in aims I and 2 as informational for cell attachment, spreading and migration are associated with the formation of a long junctional epithelial attachment, in vivo. The identification of the molecular cues which instruct cells either to attach in a stable fashion or migrate may provide new opportunities for the manipulation of cell/extracellular matrix interactions to help in the prevention and treatment of periodontal diseases. The proposed studies, utilizing biologically active macromolecules, may also lead to treatment modalities that result in more predictable regeneration of periodontal tissues.